The following is a summary of “FOXI3 haploinsufficiency contributes to low T-cell receptor excision circles and T-cell lymphopenia,” published in the December 2022 issue of Allergy & Immunology by Ghosh, et al.
By discovering a small number of copies of T-cell receptor excision circles in dried blood spots collected at birth, newborn screening can detect neonatal T-cell lymphopenia. If a screening test is positive, further diagnostic testing is necessary to identify the presence of severe combined immunodeficiency or any other causes of T-cell lymphopenia in the person. Approximately 15% of infants with a positive T-cell receptor excision circle result after the rigorous assessment are still genetically unidentified. To direct future clinical therapy and family planning it was crucial to identify the underlying genetic etiology to direct future clinical therapy and family planning. Patients with T-cell lymphopenia who lacked a precise genetic diagnosis were the focus of researchers’ efforts to clarify their genetic foundation.
To determine and clarify the genetic and molecular underpinnings, they performed functional and immunologic tests and clinical genomic testing to determine and clarify the genetic and molecular underpinnings.
They described the occurrence of heterozygous loss-of-function mutations in the forkhead box I3 transcription factor (FOXI3) in two unrelated people with nonsevere T-cell lymphopenia and aberrant T-cell receptor excision circles.
The data supported the idea that FOXI3 may be a crucial regulator of thymus development and that the haploinsufficiency of FOXI3 caused T-cell lymphopenia with varying expressivity.
Reference: jacionline.org/article/S0091-6749(22)01058-2/fulltext